The overall objective of this research project is the elucidation of the mechanism of regulation of the pyruvate dehydrogenase complex (PDC). In mammalian cells the conversion of pyruvate to acetyl-CoA by the pyruvate dehydrogenase complex serves both bioenergetic and biosynthetic roles. Regulation of this step is of central importance to the general energy balance and fuel economy of animals. Studies are being conducted to determine the mechanisms by which different metabolites alter the activity of the regulatory enzymes of these complexes, the pyruvate dehydrogenase kinase and pyruvate dehydrogenase phosphatase. Our recent objectives have focused on evaluating the relationship between catalytic function and interconvertible regulation of the mammalian pyruvate dehydrogenase complex.